COCH-Related Hearing Loss in a French Cohort: Novel Variants and Genotype–Phenotype Correlations

Heterozygous pathogenic variants in COCH (cochlin) — most abundant protein of the inner ear extracellular matrix

This retrospective multicenter French study includes 69 individuals from 20 unrelated families with DFNA9 followed over 20 years (2005–2025) through the national genetic hearing loss network (Necker + 9 CHUs). Seven known pathogenic and ten novel likely pathogenic COCH variants are reported. A domain-specific genotype–phenotype correlation is confirmed: vWFA domain variants associate with earlier onset, while LCCL domain variants link to more frequent vestibular dysfunction and later onset. Three families presented with congenital or prelingual hearing loss, an atypical DFNA9 presentation.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

COCH/DFNA9 remains a rare cause of AD hearing loss — only 20 families identified in France over 20 years — making this national cohort particularly valuable. The confirmation of prelingual/congenital onset in some vWFA2 families is an important clinical signal: do not exclude COCH from a panel based solely on early onset. The lack of functional validation for the 10 novel variants (LP, not P) tempers the immediate impact, but the ACMG rigor and cohort size for such a rare condition are convincing.